return to CHARTER site

Publication Abstract Display
Type: Poster
Title: Normal cerebrospinal fluid neurofilament light protein, but increased intrathecal immunoactivation in virally-suppressed HIV-infected patients with mild neurocognitive impairment.
Authors: Edén A, Franklin D, Fuchs D, Grant I, Letendre S, Marcotte T, Nilsson S, Price RW, Zetterberg H, Gisslén M, for the CHARTER group
Date: 03-03-2014
Abstract:Background Even in patients responding well to current antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) remain prevalent. However, it is unclear if neuronal damage continues despite effective suppression of HIV-1. The light subunit of the neurofilament protein (NFL) is a component of myelinated axons, and elevated concentrations in cerebrospinal fluid (CSF) are a sensitive marker of ongoing axonal injury in HIV-associated dementia (HAD). To investigate if milder forms of neurocognitive impairment asymptomatic neurocognitive impairment (ANI) and minor neurocognitive disorder (MND) are associated with ongoing neuronal damage, we analyzed CSF NFL in a well characterized cohort of virally-suppressed subjects on ART with or without ANI/MND. Methods In a cross-sectional analysis, subjects on ART with plasma HIV-1 RNA <50 c/ml without significant confounding conditions (e.g., current substance dependence) were identified from longitudinal studies (CHARTER and HNRC). Standardized neurocognitive performance (NP) testing was performed. Subjects were classified as NP-normal (NPN) or NP-impaired (ANI/MND) based upon demographically-adjusted norms. Subjects were selected to yield approximately equal samples of NPN, ANI, and MND. CSF concentrations of NFL were measured by an enzymatic 2-site quantitative immunoassay (UmanDiagnostics, Umea, Sweden). CSF neopterin was measured by ELISA. Continuous variables were log10 transformed where appropriate. For two group comparisons, Mann- Whitney-U-test was used. The relationship between CSF NFL levels and age in the two groups were analyzed with a linear mixed effects model. Correlations were calculated using Pearson correlation coefficients test. Results 100 (91% male) subjects were included in the analysis, 29 NPN and 71 with ANI/MND (ANI=38; MND=33). Median (IQR) age was 47 (41-54) years, with current CD4+ 524 (359-771) and nadir 72 (10-224) x106 cells/l. 97% of participants also had CSF HIV-1 RNA <50 c/ml (remaining 3 subjects < 125 c/ml). No statistically significant difference was found in NFL between the NPN and ANI/MND groups. We found no correlation between CD4 cell count or CD4 nadir and NFL, however CSF neopterin was significantly correlated to NFL in the whole study population (r=0.21; p=0.035) and CSF neopterin was higher in the ANI/MND group (median 7.3, IQR 4.9-12 nmol/l) than in the NPN group (median 4.8, IQR 4.7-7-4 nmol/l) (p<0,01). Conclusions In this cross sectional analysis we found no difference in NFL in subjects with ANI/MND compared to subjects without neurocognitive impairment. Interestingly, CSF neopterin was higher in the ANI/MND group indicating an association between increased intrathecal immunoactivation and neurocognitive impairment in patients on ART.

return to publications listing